Multi-lumen biologic-delivering device

ABSTRACT

Arrangements and methods for delivering bioactive agents and/or cells into an extended volume of tissue are disclosed. In one embodiment, a cell-delivering needle arrangement has a tube positioned within a tube and fixedly attached to a wall thereof. In one exemplary method, a cell-delivering needle is advanced into tissue, a suspension of cells is passed through a first lumen and out of side ports, and a suspension of cells is passed through a second lumen and out of a distal opening. Other embodiments are disclosed.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.61/672,496, filed Jul. 17, 2012, which is hereby incorporated byreference in its entirety.

FIELD

The present invention relates generally to biologic-delivering needlesand cannulas.

BACKGROUND

Critical limb ischemia (also referred to as “CLI”) is a severeobstruction of the arteries in the extremities of the body, often thelower extremities including the leg, that results in a significantlyreduced blood-flow. CLI can result in severe pain, skin ulcers or soresand, if left untreated, may result in amputation of the affected limb.CLI is unlikely to improve on its own and therefore often requiresintervention from a medical professional.

Various bioactive agents and biologic materials such as cells, includingstem cells, are currently being researched and used to treat CLI. Insome of these treatments, a series of injections are made along thelength of the patient's limb. Due to limited perfusion of the bioactiveagent and/or biologic material, a large number of injections are oftenrequired to sufficiently spread the bioactive agent and/or biologicmaterial throughout the tissue of the limb.

There exists a need for needle arrangements and associated methods thatcan deliver bioactive agents and/or biologic materials into an extendedvolume of tissue in a patient. Similarly, there exists a need for needlearrangements and associated methods that can sufficiently perfusebioactive agents and/or biologic materials into tissue.

SUMMARY

In certain aspects, the present disclosure provides devices and methodsfor the delivery of biologic materials and/or bioactive agents into anextended volume of tissue. In accordance with some forms of thedisclosure, such devices and methods are arranged to deliver asuspension of biologic material from a first lumen and a second lumen.In one embodiment, a method of delivering biologic material into anextended volume of tissue of a patient comprises: advancing a distal endregion of a biologic-material-delivering needle having an elongated bodydefining a first lumen, a second lumen, a plurality of side portsassociated with the first lumen, an end port associated with the secondlumen, and a tissue-penetrating tip through the skin of the patient;passing a first suspension of biologic material through the first lumenand out of the side ports associated with the first lumen to release abiologic material from the side ports towards tissue adjacent to theelongated body; and passing a second suspension of biologic materialthrough the second lumen and out of the end port associated with thesecond lumen to release a biologic material from the end port intotissue of the patient. In some instances, the second lumen is defined bya second elongate body positioned within the first lumen and fixedlycoupled to a wall thereof. Additionally, in some aspects, the pluralityof side ports are positioned around the periphery of the elongated body.The method may also comprise withdrawing thebiologic-material-delivering needle while passing a suspension ofbiologic material into the biologic-material-delivering needle tract. Insome instances, the biologic material comprises a plurality of cells.

In one embodiment, the present disclosure teaches a needle comprising aneedle body having a proximal end region, a distal end region, and asidewall; the needle body defining a first lumen extending from theproximal end region to the distal end region; the first lumenterminating in a closed distal end and communicating with a plurality ofports defined by the sidewall; the needle body defining a second lumenextending from the proximal end region to the distal end region andcommunicating with a distal opening in the distal end region; and thedistal end region having a tissue-penetrating tip. In some instances,the first lumen and a second lumen are fixedly positioned to oneanother. Additionally, in some aspects, the plurality of side ports arepositioned around the periphery of the elongated body. In someembodiments, the second lumen is positioned within the first lumen.

In one aspect, the present disclosure provides a fluid delivering needlecomprising a needle body having a proximal end region, a distal endregion, a first elongated body, and a second elongated body; the firstelongated body having a sidewall defining a first lumen extending fromthe proximal end region to the distal end region; the first lumenterminating in a closed distal end and communicating with a plurality ofports defined by the sidewall and positioned around the periphery of thefirst elongated body; the second elongated body positioned within thefirst lumen and fixedly coupled to a wall thereof; the second elongatedbody defining a second lumen extending from the proximal end region tothe distal end region and communicating with a distal opening in thedistal end region; and the distal end region of the needle body having atissue-penetrating needle tip. In some instances, the side ports have across-sectional area that is smaller than a cross-sectional area of thedistal opening. Additionally, in some aspects, the second lumen has across-sectional area that is smaller than a cross-sectional area of thefirst lumen. In some embodiments, the needle further comprises a plugclosing the distal end of the first lumen.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a cross-sectional, plan view of a cell-delivering needle.

FIG. 2 is a perspective view of a distal end region of thecell-delivering needle illustrated in FIG. 1.

FIG. 3 is a cross-sectional view of the elongated needle bodyillustrated in FIG. 1.

FIG. 4 is a cross-sectional, plan view of a cell-delivering needle.

FIG. 5 is a perspective view of a distal end region of thecell-delivering needle illustrated in FIG. 4.

FIG. 6 is a cross-sectional view of the elongated needle bodyillustrated in FIG. 4.

FIG. 7 is a cross-sectional, plan view of a cell-delivering needle.

FIG. 8 is a cross-sectional, plan view of a cell-delivering needle.

FIG. 9 is a perspective view of a distal end region of a cell-deliveringneedle.

FIG. 10 is a cross-sectional, plan view of a cell-delivering needle.

FIG. 11 is a perspective view of the cell-delivering needle illustratedin FIG. 10.

FIG. 12 is a cross-sectional view of the elongated needle bodyillustrated in FIG. 10.

FIG. 13 illustrates the body of a patient.

FIG. 14 illustrates a cross-sectional view of a leg of a patient.

FIG. 15 illustrates a cross-sectional view of a leg of a patient with acell-delivering needle assembly being brought into proximity therewith.

FIG. 16 illustrates the insertion of a cell-delivering needle assemblyinto a leg of a patient and the delivery of cells.

FIG. 17 illustrates withdrawing a cell-delivering needle assembly from aleg of a patient.

DESCRIPTION OF THE ILLUSTRATED EMBODIMENTS

For the purposes of promoting an understanding of the principles of thedisclosure, reference will now be made to the embodiments illustrated inthe drawings and specific language will be used to describe the same. Itwill nevertheless be understood that no limitation of the scope of theclaims is thereby intended, and alterations and modifications in theillustrated device, and further applications of the principles of thedisclosure as illustrated therein are herein contemplated as wouldnormally occur to one skilled in the art to which the disclosurerelates.

With respect to the specification and claims, it should be noted thatthe singular forms “a”, “an”, “the”, and the like include pluralreferents unless expressly discussed otherwise. As an illustration,references to “a device” or “the device” include one or more of suchdevices and equivalents thereof. It also should be noted thatdirectional terms, such as “up”, “down”, “top”, “bottom”, and the like,are used herein solely for the convenience of the reader in order to aidin the reader's understanding of the illustrated embodiments, and it isnot the intent that the use of these directional terms in any mannerlimit the described, illustrated, and/or claimed features to a specificdirection and/or orientation.

The reference numerals in the following description have been organizedto aid the reader in quickly identifying the drawings where variouscomponents are first shown. In particular, the drawing in which anelement first appears is typically indicated by the left-most digit(s)in the corresponding reference number. For example, an elementidentified by a “100” series reference numeral will likely first appearin FIG. 1, an element identified by a “200” series reference numeralwill likely first appear in FIG. 2, and so on.

The disclosed embodiments and variations thereof may be used to deliverbioactive agents, biologic materials such as porcine small intestinalsubmucosa (SIS) and/or a plurality of cells, such as stem cells, such asto locations within soft tissue anywhere in the body of a human and/orveterinary patient. For instance, the disclosed embodiments may be usedto deliver cells to tissue within a patient's extremities such as a leg,or to an internal organ such as the kidney or pancreas. For simplicity,the following embodiments will be discussed with reference to theinjection of a suspension of cells into tissue of a human patient. Someportions will discuss exemplary arrangements and/or methods withspecific reference to a patient's leg; however, it is not intended thatthe present disclosure be limited to such. Similarly, reference to acell-delivering needle is not intended to limit the device to only thedelivery of cells. As mentioned, other biologic materials, such as SIS,may be delivered with the disclosed embodiments.

FIGS. 1, 2 and 3 illustrate views of one embodiment of a cell-deliveringneedle 100. The cell-delivering needle 100 can comprise a distal endregion 102, a proximal end region 104, an elongated needle body 106 anda connector 108.

The elongated needle body 106 of the cell-delivering needle 100 cancomprise an outer tube 109 having a first sidewall portion 110 thatdefines a first lumen 112. The first lumen 112 can be influid-communication with a first lumen proximal opening 114 positionedin and/or near the proximal end region 104 of the cell-delivering needle100. Additionally, the first lumen 112 can be in fluid-communicationwith a plurality of side ports 116 that are defined by the firstsidewall portion 110 of the outer tube 109 of the elongated needle body106. In some instances, the side ports 116 can be positioned in and/ornear the distal end region 102 of the cell-delivering needle 100. Adistal end of the first lumen 112 defined by the first sidewall portion110 can contain a plug 118 arranged to block fluid flow from exiting theend of the first lumen 112.

The cell-delivering needle 100 can comprise an inner tube 119 having asecond sidewall portion 120 defining a second lumen 122. The secondlumen 122 can be in fluid-communication with a second lumen proximalopening 124 positioned in and/or near the proximal end region 104 of thecell-delivering needle 100. The second lumen 122 can also be influid-communication with a distal opening 126 positioned in and/or nearthe distal end region 102 of the cell-delivering needle 100. In someinstances, the second sidewall portion 120 of the inner tube 119 isfixedly coupled to the first sidewall portion 110 of the outer tube 109along a coupling surface 128. For example, the second sidewall portion120 may be welded and/or adhesively attached to an inner wall of thefirst lumen 112, to name a few non-limiting examples.

In some instances the elongated needle body 106 of the cell-deliveringneedle 100 resembles an inner tube 119 positioned within an outer tube109, the inner tube 119 having a maximum outer dimension smaller thanthe maximum outer dimension of the lumen (such as the first lumen 112)defined by the outer tube 109. As discussed above, the inner tube 119can be fixedly attached to a wall of a lumen (such as the first lumen112) defined by the outer tube 109. Alternatively, in some instances,the inner tube 119 is positioned within the outer tube 109 and has anannular space between an outer wall of the inner tube 119 and an innerwall of the outer tube 109. For example, the annular space may surroundthe inner tube 119.

The cell-delivering needle 100 may have a tissue-penetrating tip 130positioned in the distal end region 102. The tissue-penetrating tip 130may comprise portions of the first sidewall portion 110 and/or thesecond sidewall portion 120. The tissue-penetrating tip 130 may resembleany tip known to those of ordinary skill in the art to be suitable topenetrate tissue of a human and/or a veterinary patient. For example,the tissue-penetrating tip 130 may be a needle tip and/or have a singlebevel and/or a triple bevel, to name just a few non-limiting examples.

The connector 108 positioned in and/or near a proximal end region 104 ofthe cell-delivering needle 100 may comprise a first coupling portion 140and/or a second coupling portion 142 arranged to couple afluid-supplying device and/or a fluid-pressurizing device, such as asyringe, to the cell-delivering needle 100. For example, the firstcoupling portion 140 of the first connector 108 may fluidly couple afirst syringe for fluid-communication with the first lumen 112.Similarly, for example, the second coupling portion 142 of the connector108 may fluidly couple a second syringe for fluid-communication with thesecond lumen 122. In some instances, the first coupling portion 140and/or second coupling portion 142 may be arranged for the coupling ofmore than one lumen for fluid-communication with a fluid-supplyingand/or a fluid-pressurizing device.

To illustrate the fluid-communication between the cell-delivering needle100 and a fluid-supplying and/or a fluid-pressurizing device such as asyringe, a fluid supplied by a first syringe in fluid-communication withthe cell-delivering needle 100 can travel through the connector 108,through the first lumen 112, and out of side ports 116 in a directiontowards tissue adjacent to a portion of the cell-delivering needle 100,such as tissue adjacent to the elongated needle body 106. Similarly, afluid supplied by a second syringe and/or a first syringe fluidlycoupled to the second lumen 122 of the cell-delivering needle 100 cantravel through the connector 108, through the second lumen 122, and outof the distal opening 126.

In some embodiments, the side ports 116 may be positioned around theperiphery of a portion of the cell-delivering needle 100 such as theelongated needle body 106. For example, the side ports 116 may bepositioned around the elongated needle body 106 in a repeating pattern.In some instances, the side ports 116 are helically wound around theelongated needle body 106. Alternatively or additionally, a number ofthe side ports 116 may be placed in a non-pattern fashion (e.g., in arandom fashion) around the periphery of the elongated needle body 106 ofthe cell-delivering needle 100.

In some embodiments, some portions of the cell-delivering needle 100 mayhave more side ports 116 than other portions. For example, the distalend region 102 of the cell-delivering needle 100 may have a greaternumber of side ports 116 than portions of the cell-delivering needle 100positioned proximal of the distal end region 102. Having a greaterconcentration, such as a greater number, of side ports 116 in a portionof the cell-delivering needle 100 may be preferred to deliver additionalcells to a selected area of tissue inside of the patient.

One or more of the side ports 116 of the cell-delivering needle 100 maybe of a different size and/or shape. For example, some of the side ports116 may have a larger cross-sectional area than other side ports 116.Additionally, some of the side ports 116 may have a circularcross-section while others have an oblong cross-section.

In some embodiments the side ports 116 are positioned around the outsideof the elongated needle body 106 so as to deliver a fluid suspension ofcells towards tissue adjacent to the elongated needle body 106 of thecell-delivering needle 100. For example, a fluid suspension deliveredfrom the side ports 116 and/or the first lumen 112 may travel in aradial direction away from the cell-delivering needle 100.

The side ports 116 may also be positioned in various angles with respectto a longitudinal axis of the cell-delivering needle 100 and/or alongitudinal axis of a portion of the cell-delivering needle 100, suchas the longitudinal axis 107 of the elongated needle body 106. Forinstance, some side ports 116 may be arranged, such as by being angled,to direct a suspension of cells in a longitudinal direction (e.g., alongthe length of the portion of the cell-delivering needle 100) as well asin a radial direction away from the cell-delivering needle 100.Similarly, some side ports 116 may direct a suspension of cells in adirection substantially tangential to a circular cross-section of theelongated needle body 106. In some instances, multiple side ports 116may direct a suspension of cells towards tissue positioned between theside ports 116, and in some instances some side ports 116 may direct asuspension of cells away from other side ports 116.

In some embodiments, the distal opening 126 may be positioned in and/ornear the tissue-penetrating tip 130 of the cell-delivering needle 100.Additionally, the distal opening 126 may be adjacent to and/or distal ofthe tissue-penetrating tip 130. In some instances, the distal opening126 and/or the second lumen 122 may be arranged to deliver a suspensionof cells to tissue located adjacent to the tissue-penetrating tip 130.Additionally, the distal opening 126 and/or the second lumen 122 may bearranged so as to deliver a suspension of cells in a directionsubstantially along the length of the cell-delivering needle 100 and/orthe elongated needle body 106. For example, a suspension of cells maytravel through the second lumen 122 along the length of the elongatedneedle body 106 and exit the distal opening 126 in a direction along thelongitudinal axis 107 of the elongated needle body 106. The distalopening 126 and/or the second lumen 122 may also be arranged to direct asuspension of cells in a direction transverse to the longitudinal axis107 of the elongated needle body 106.

The plug 118 positioned inside of the first lumen 112 may contactportions of the second sidewall portion 120. As illustrated in FIGS. 1and 2, the plug 118 may comprise a cylinder having a semi-circularcross-section with a recess for receiving the second sidewall portion120 and the second lumen 122. In some embodiments, the plug 118 isarranged to block fluid flow out of the distal end of the first lumen112. For example, a fluid may enter the first lumen 112 through thefirst lumen proximal opening 114 and exit through the side ports 116 butbe prevented from exiting the distal end of the first lumen 112 due tothe positioning of the plug 118 within the first lumen 112.Additionally, in some instances, the plug 118 can be arranged so as toallow pressurization of the first lumen 112 so as to increase thevelocity and/or the pressure of a suspension of cells exiting the sideports 116, which is believed to increase the perfusion of the cells intoadjacent tissue and beyond.

As illustrated in FIG. 3, the inner tube 119 may be smaller incross-sectional area than the outer tube 109. In some instances, thiscan result in greater pressure loss in fluid traveling through thesecond lumen 122 as compared to fluid traveling through the first lumen112. Pressure loss for fluid traveling through tubes, pipes, ducts, etc.is often discussed in terms of major loss and minor loss. Major loss isthe pressure loss due to friction within the tube. Minor loss is due tochanges in the velocity of the moving fluid. The major loss portion ofpressure loss of a fluid traveling through a tube can be approximated bythe equation:

p _(loss)=λ(l/d _(h))(ρv ²/2)  (1)

-   -   where    -   ρ_(loss)=pressure loss (Pa, N/m²)    -   λ=friction coefficient    -   l=length of tube (m)    -   d_(h)=hydraulic diameter (m)    -   ρ=density of the fluid (kg/m³)    -   v=flow velocity (m/s)        As can be understood by the approximation above, decreasing the        diameter of the fluid-carrying tube will increase the pressure        loss in the moving fluid. Similarly, increasing the length of        fluid-carrying tube, increasing the friction coefficient (such        as by increasing the surface roughness of the tube), increasing        the density of the fluid, and/or increasing the velocity of the        fluid moving through the tube will increase the pressure loss in        the moving fluid.

In some instances it may be preferred to arrange the cell-deliveringneedle 100 so as to deliver a suspension of cells at a higher pressureand/or a higher velocity from one lumen and/or outlet(s) (e.g., thefirst lumen 112 and/or the side ports 116) than from another lumenand/or outlet(s) (e.g., the second lumen 122 and/or the distal opening126). For example, for a sufficient perfusion of a suspension of cellsinto the tissue of a patient, one or more suspensions of cells may needto be delivered at a higher pressure and/or a higher velocity from theside ports 116 than from the distal opening 126. In some instances, thedistal end region 102 of the cell-delivering needle 100 may bepositioned adjacent to sensitive tissue such as a nerve bundle, andtherefore it is desired to deliver the suspension of cells towards thesensitive tissue at a lower pressure and/or velocity than suspensions ofcells being delivered to less sensitive tissue so as to decrease thelikelihood of injury to the sensitive tissue. As discussed above, thelength, hydraulic diameter, and/or surface roughness of a lumen may bearranged so as to achieve a desired pressure loss in the suspension ofcells traveling through the lumen. Additionally, one may change thedensity of a fluid suspension, the velocity of a fluid suspensiontraveling through a lumen, and/or the type of fluid flow (laminar,transient, or turbulent) moving through the lumen to achieve a desiredpressure loss. These changes may be made in addition to or as analternative to arranging the size and shape of the sideports so as toachieve a desired pressure and/or velocity of cells exiting thesideports.

In some instances, the pressure inside of one or more lumens may bemonitored. An operator may desire the pressure in a lumen to remainbelow a certain threshold so as to avoid damaging the cells travelingthrough the cell-delivering needle. Additionally, as will be appreciatedby a person of ordinary skill in the art, the cell-delivering needle maybe arranged so as to operate with some minimum pressure inside one ormore of the lumens. For example, the sideports and/or lumens may bearranged such that a certain minimum pressure is required at a locationwithin one or more of the lumens to achieve the desired delivery ofcells from the cell-delivering needle.

In some applications, the cell-delivering needle may have built-inpressure monitoring in one or more lumens. For example, pressure sensorsand/or gauges may be in communication with one or more lumens of theneedle. The signals from the pressure sensors can used to adjust thevolume and/or pressure of fluid being supplied to the needle (e.g., acontrol system for operating an actuated pressurizing device usingfeedback from pressure sensors). Similarly, in some embodiments, flowsensors may be used to monitor the amount of fluid flowing through oneor more lumens of the needle.

The first coupling portion 140 and/or the second coupling portion 142 ofthe connector 108 positioned in and/or near the proximal end region 104of the cell-delivering needle 100 may be of a standard type known andused in the medical profession. For instance the first coupling portion140 and/or the second coupling portion 142 may be of the Luer Lock typeand arranged to couple a syringe and/or other pressurizing device withthe cell-delivering needle 100.

FIG. 4 illustrates another embodiment of a cell-delivering needle 400.Similar to the cell-delivering needle 100 illustrated in FIGS. 1, 2, and3, cell-delivering needle 400 comprises a distal end region 402, aproximal end region 404, an elongated needle body 406, and a connector408 comprising a first coupling portion 440 and/or a second couplingportion 442. The cell-delivering needle 400 can comprise a firstsidewall portion 410 and a second sidewall portion 420 defining a firstlumen 412 and a second lumen 422. The first lumen 412 opening to a firstlumen proximal opening 414 and side ports 416, and the second lumen 422opening to a second lumen proximal opening 424 and a distal opening 426.A plug 418 can be positioned in a distal end of the first lumen 412 soas to prevent a suspension of cells from exiting a distal end of thefirst lumen 412, and the cell-delivering needle 400 can comprise atissue-penetrating tip 430 positioned in the distal end region 402. Insome embodiments the tissue-penetrating tip 430 and distal opening 426of the second lumen 422 are adjacent to one another.

The second lumen 422 can be positioned within the first lumen 412, andthe second lumen 422 and first lumen 412 can share a sidewall portion.For example, as illustrated in FIG. 4, the second lumen 422 may bedefined by both the second sidewall portion 420 and the first sidewallportion 410. The second sidewall portion 420 of the cell-deliveringneedle 400 illustrated in FIG. 4 in some instances may comprise anadditional portion of the elongated needle body 406 such as an extensionfrom the first sidewall portion 410 of the cell-delivering needle 400.

FIG. 5 illustrates a perspective view of one embodiment of acell-delivering needle such as that illustrated in FIG. 4. In thisillustration, the second sidewall portion 520 of the elongated needlebody 506 is arranged such that the first lumen 512 does not extendsubstantially around the second lumen 522. As is shown in the figure,the plug 518 in the distal end region 502 does not have a recess for thesecond sidewall portion 520 and/or the second lumen 522. The first lumen512, the second lumen 522, the plug 518, and/or the distal opening 526can have circular cross-sections. In some instances, the second sidewallportion 520 can comprise extensions of the first sidewall portion 510.

FIG. 6 illustrates a cross-sectional view of an elongated needle body606 of another embodiment of a cell-delivering needle, such as thecell-delivering needle 400 illustrated in FIG. 4. In this illustration,the second side wall portion 620 forms a loop within the first lumen 612defined by the first sidewall portion 610. The second lumen 622 can bepositioned inside of the first lumen 612 and defined by both the secondsidewall portion 620 and the first sidewall portion 610.

As illustrated in this and other embodiments, the nested placement ofthe second lumen (e.g., second lumen 422) within the first lumen (e.g.,first lumen 412) and/or sharing of sidewalls between the second and/orfirst lumen can provide a number of benefits. For instance, positioningone lumen inside of the other can allow for a smaller maximum outerdimension for the cell-delivering needle. In embodiments that sharesidewall portions, the overall needle cross-sectional area may bereduced, as compared to embodiments that do not share sidewall portions,while maintaining the cross-sectional areas of the lumens. Additionally,positioning the second lumen inside of the first lumen and/or along asidewall thereof can allow for the positioning of the distal openingcloser to the tissue-penetrating tip of the cell-delivering needle.

Other benefits of positioning the second lumen within the first lumenand/or the sharing of sidewalls therewith will be apparent to those ofordinary skill in the art. For example, the sharing of sidewalls betweenlumens can decrease the amount of material necessary to form theelongated needle body and/or both lumens.

FIGS. 7 and 8 illustrate additional embodiments of a cell-deliveringneedle. In these embodiments, the second lumen proximal opening 724, 824is in fluid communication with the first lumen 712, 812. Thisarrangement can allow for a single fluid-supplying device and/orfluid-pressurizing device to provide a suspension of cells to the firstlumen 712, 812 and the second lumen 722, 822. In some instances asuspension of cells is provided to the first lumen 712, 812 and thesecond lumen 722, 822 simultaneously.

This arrangement can also allow for a suspension of cells to bedelivered from the distal opening 726, 826 at a pressure lower than asuspension of cells delivered from the side ports 716, 816. In someinstances the hydraulic diameter of the second lumen 722, 822 may beless than the hydraulic diameter of the first lumen 712, 812 and cause agreater pressure loss greater in the second lumen 722, 822 than in thefirst lumen 712, 812. For example, the inner tube 719 can have a maximumouter dimension smaller than the maximum outer dimension of the firstlumen 712 and can be arranged so as to deliver a suspension of cellsfrom the distal opening 726 at a pressure lower than a suspension ofcells delivered from one or more side ports 716. Additionally, the sideports 716, 816 and/or the distal opening 726, 826 may be arranged so asto provide additional pressure loss (minor losses) to the fluidsuspension of cells being delivered from the side ports 716, 816 and/orthe distal opening 726, 826.

The cell-delivering needle 700, 800 can have a connector 708, 808positioned at a proximal end region 704, 804 of the cell-deliveringneedle 700, 800. The connector 708, 808 can have a coupling portion 740,840 arranged to couple a fluid-supplying device and/orfluid-pressurizing device to the cell-delivering needle 700, 800. Theconnector 708, 808 and/or the coupling portion 740, 840 can be arrangedto fluidly-couple the fluid-supplying device and/or fluid-pressurizingdevice to the first lumen 712, 812 and the second lumen 722, 822.

FIG. 9 illustrates a perspective view of a distal end region 902 of acell-delivering needle. A first lumen 912 defined by the first sidewallportion 910 terminates in a closed distal end 932 in a beveled region934 adjacent to a tissue-penetrating tip 930. In some instances, thedistal end of the first lumen 912 is closed by a crimped portion of thefirst sidewall portion 910 in the beveled region 934. In someembodiments the distal opening 926 of the second lumen 922 is positionedadjacent to the tissue-penetrating tip 930 and the closed distal end 932of the first lumen 912.

FIGS. 10-12 illustrate another embodiment of a cell-delivering needle.Similar to some of the embodiments disclosed above, the cell-deliveringneedle 1000 has an elongated needle body 1006 and comprises an outertube 1009 and an inner tube 1019, the outer tube 1009 having a firstsidewall portion 1010 that defines a plurality of sideports 1016 spacedaround the circumference of the outer tube 1009. In some instances, theinner tube 1019 is positioned concentrically within the outer tube 1009so as to have a co-axial arrangement. A plug 1018 is positioned aroundthe circumference of the inner tube 1019 to seal the distal end region1002 of the first lumen 1012.

FIG. 13 illustrates a plan view of the body of a patient 1300. Thedisclosed embodiments of cell-delivering needles may be used to delivera plurality of cells and/or a biologic agent to organs or soft tissueanywhere in the body. In some instances a cell-delivering needle may beused to treat tissue positioned inside of a patient's leg 1302. Morespecifically in some instances the cell delivering needle is used totreat tissue positioned within the calf portion 1304 of the leg 1302.

The various embodiments of the cell-delivering needle and portionsthereof disclosed above may be constructed from materials such as thoseknown in the art to be used for construction of needles and/or cannulas.For example, the elongated needle body and portions thereof may beformed from materials commonly used to manufacture needles and/orcannulas, such as stainless and/or surgical steel to name a fewnon-limiting examples. Portions of the cell-delivering needle, such asthe connector, may also be formed of polymer materials such aspolypropylene and/or polyethylene, just to name a few non-limitingexamples.

Additionally, the various embodiments of the cell-delivering needle andportions disclosed above may be formed by any method known by those ofordinary skill in the art. For example, the cell-delivering needle 100illustrated in FIG. 1 may be constructed by welding portions of theinner tube 119 to the outer tube 109. Additionally or alternatively,portions of the inner tube 119 and/or outer tube 109 may be affixedrelative to one another by the connector 108. In some embodiments, theplug 118 in the first lumen 112 fixedly attaches the outer tube 109 tothe inner tube 119. Other methods known by those of ordinary skill inthe art used to construct multi-lumen needles, such as swaging one tubeinside of another tube, can be used as well.

Method of Use

Various embodiments of the present disclosure are arranged to deliver asuspension of cells to tissue within a patient's body. In someinstances, the present disclosure provides embodiments arranged todeliver a suspension of cells to tissue, such as muscle, positioned atvarious depths beneath the surface of the patient's skin. Exemplarymethods of delivering cells into an extended volume of tissue in apatient will now be discussed. Some of the disclosed embodiments will beused to illustrate methods of delivering cells into the tissue within aleg of a patient, but no limitation to such is intended.

FIG. 14 illustrates a cross-sectional view of the calf portion 1304 ofthe leg 1302 of the body of a patient 1300. The skin 1400 of the leg1302 encompasses the tibia 1402, and the fibula 1404, as well as muscletissue, vessels, and nerves.

When discussing the muscles of the leg 1302, the muscles are oftendivided into deep layer muscle 1410 and superficial layer muscle 1412.The deep layer muscle 1410 resides further beneath the surface of theskin 1400 than the superficial layer muscle 1412. For example, thesoleus muscle 1414 is a deep layer muscle 1410, and the gastrocnemiusmuscle 1416 is a superficial layer muscle 1412. Both the soleus muscle1414 and the gastrocnemius muscle 1416 are located posteriorly of thetibia 1402 and the fibula 1404. In the anterior portion of the leg 1302is the tibialis anterior muscle 1418 that is located mostly laterally ofthe tibia 1402. Posteriorly of the tibialis anterior muscle 1418 andlaterally of the fibula 1404 is the fibularis (aka: the peroneus) brevisand longus muscles 1420.

There are a number of vessels located in the calf portion 1304 of theleg 1302. Positioned between the solues muscle 1414 and the tibialisanterior muscle 1418 are the peroneal artery 1430, the peroneal vein1432, the posterior tibial artery 1434, and the posterior tibial vein1436. The leg 1302 also has the small sapheous vein 1438 that is locatedin the superficial posterior portion of the leg 1302.

Also of note for the present disclosure are various nerves located inthe calf portion 1304 of the leg 1302. The tibial nerve 1450 ispositioned between the soleus muscle 1414 and the tibialis anteriormuscle 1418. In the superficial posterior portion of the leg 1302 arethe medial cutaneous nerve 1452 and the lateral cutaneous nerve 1454.

FIG. 15 illustrates an exemplary cell-delivering needle assembly 1500.The cell-delivering needle assembly 1500 can comprise a cell-deliveringneedle 1501 and a first syringe 1550 and/or a second syringe 1552. Thecell-delivering needle 1501 can also have a connector 1508 for couplingthe cell-delivering needle 1501 to the first syringe 1550 and/or thesecond syringe 1552. The connector 1508 can allow the fluidcommunication of the first lumen 1512 and side ports 1516 with the firstsyringe 1550 and the fluid communication of the second lumen 1522 anddistal opening 1526 with the second syringe 1552.

As illustrated in FIG. 15, the exemplary cell-delivering needle assembly1500 is positioned relative to the leg 1302 of a patient with thetissue-penetrating tip 1530 positioned adjacent to the skin 1400 of aleg 1302. The cell-delivering needle assembly 1500 may be inserted in avariety of directions towards a deep layer muscle 1410. For example, thecell-delivering needle assembly 1500 may be inserted into a posteriorportion of the leg 1302 along a posterior to anterior direction.Alternatively, the cell-delivering needle assembly 1500 may be insertedinto an anterior portion of the leg 1302 along a anterior to posteriordirection.

The cell-delivering needle assembly 1500 can be advanced in a posteriorto anterior direction through the skin 1400 of the patient medially ofthe medial cutaneous nerve 1452. After penetrating the skin 1400, anoperator can check the positioning of the distal end region (such as thetissue-penetrating tip 1530) of the cell-delivering needle 1501. Forexample, the operator may check whether the tissue-penetrating tip 1530of the cell-delivering needle 1501 has penetrated a blood vessel such asthe small saphenous vein 1438 in the superficial posterior portion ofthe leg 1302. One way an operator may check is by applying a negativepressure, by use of the syringe, to the first lumen 1512 and/or secondlumen 1522. If the operator observes flashback (i.e., a flash of bloodthat is observed when a needle punctures a blood vessel) then thetissue-penetrating tip 1530 has punctured a blood vessel. Alternativelyor additionally, imaging such as x-ray and/or ultrasound may be used toconfirm the proper positioning of the distal end region of thecell-delivering needle 1501.

The cell-delivering needle 1501 portion of the cell-delivering needleassembly 1500 may then be advanced through the gastrocnemius muscle 1416and the soleus muscle 1414 following a path towards the tibial nerve1450. In some instances, the cell-delivering needle 1501 is advanceduntil the tissue-penetrating tip 1530 is positioned posteriorly of thetibial nerve 1450. Additionally, as the cell-delivering needle 1501 isadvanced, a suspension of cells may be delivered through the side ports1516 and/or the distal opening 1526 of the cell-delivering needle 1501.

The cell-delivering needle 1501 is advanced to a desired position in thetissue, such as that illustrated in FIG. 16. In some instances, thedistal opening 1526 and/or side ports 1516 may become clogged withtissue, such as skin and/or muscle tissue. To check the patency of theside ports 1516 and/or the distal opening 1526, the user may applynegative pressure to the first lumen 1512 and/or second lumen 1522 suchas by use of the first and/or second syringe 1550, 1552.

After the cell-delivering needle 1501 is in position, a suspension ofcells can be delivered. A suspension of cells can be delivered throughthe side ports 1516 and/or the distal opening 1526 of thecell-delivering needle 1501. Cells can be delivered from the side ports1516 into deep layer muscle 1410 and/or superficial layer muscle 1412.For example, cells may be delivered into the soleus muscle 1414, and/orthe gastrocnemius muscle 1416. In some embodiments, cells delivered fromthe side ports 1516 perfuse into the tissue adjacent to the side ports1516 and beyond the needle tract.

In some embodiments, a first suspension of cells is delivered throughthe first lumen 1512 and the side ports 1516 and a second suspension ofcells is delivered through the second lumen 1522 and the distal opening1526. In some embodiments, the suspensions delivered through the firstand second lumens 1512, 1522 and the side ports 1516 and distal opening1526 are the same.

Additionally or alternatively, cells can be delivered from the distalopening 1526 towards the tibial nerve 1450, the peroneal artery/vein1430, 1432, and/or the posterior tibial artery/vein 1434, 1436. In someinstances, it is preferred to deliver a plurality of cells towards thetibial nerve 1450 so as to promote innervation. Additionally, deliveringcells near the peroneal artery/vein 1430, 1432 and/or the posteriortibial artery/vein 1434, 1436 may promote angiogenesis (i.e., vesselformation) in tissue, such as the soleus muscle 1414.

After a suspension of cells has been delivered from the side ports 1516and/or the distal opening 1526, the cell-delivering needle 1501 may bewithdrawn. As the cell-delivering needle 1501 is being withdrawn,additional suspensions of cells may be delivered from the side ports1516 and/or the distal opening 1526. For example, an additionalsuspension of cells may be delivered from the distal opening 1526 and/orthe side ports 1516 into the needle tract.

The cell-delivering needle 1501 may also be flushed with a salinesolution before, during and or after the various stages disclosed above.For example, the cell-delivering needle 1501 may be flushed with salinebefore the tissue-penetrating tip 1530 is inserted into tissue.Similarly, the cell-delivering needle 1501 may be flushed with saline totransport cells through and/or from the first lumen 1512, second lumen1522, side ports 1516, and/or distal opening 1526.

While the disclosure has been illustrated and described in detail in thedrawings and foregoing description, the same is to be considered asillustrative and not restrictive in character, it being understood thatthe preferred embodiment has been shown and described and that allchanges and modifications that come within the spirit of the disclosureare desired to be protected. It will be evident from the specificationthat aspects or features discussed in one context or embodiment will beapplicable in other contexts or embodiments.

What is claimed is:
 1. A method of delivering a biologic material intoan extended volume of tissue of a patient, comprising: advancing adistal end region of a biologic-material-delivering needle having anelongated body defining a first lumen, a second lumen, a plurality ofside ports associated with said first lumen, an end port associated withsaid second lumen, and a tissue-penetrating tip through the skin of thepatient; passing a first suspension of biologic material through saidfirst lumen and out of said side ports associated with said first lumento release a biologic material from said side ports towards tissueadjacent to said elongated body; and passing a second suspension ofbiologic material through said second lumen and out of said end portassociated with said second lumen to release a biologic material fromsaid end port into tissue of the patient.
 2. The method of claim 1,wherein: said biologic material comprises cells.
 3. The method of claim1, wherein: said second lumen is defined by a second elongate bodypositioned within said first lumen and said second elongate body issurrounded by an annular space.
 4. The method of claim 1, wherein: saidsecond lumen is defined by a second elongate body positioned within saidfirst lumen and fixedly coupled to a wall thereof.
 5. The method ofclaim 1, further comprising: withdrawing saidbiologic-material-delivering needle while passing a suspension ofbiologic material into the biologic-material-delivering needle tract. 6.The method of claim 1, wherein: said plurality of side ports arepositioned around the periphery of the elongated body.
 7. The method ofclaim 5, wherein: passing a suspension of biologic material into thebiologic material-delivery needle that comprises passing a suspension ofbiologic material through said second lumen and out of said end portassociated with said second lumen.
 8. The method of claim 7, furthercomprising: passing a suspension of biologic material through said firstlumen and out of said side ports associated with said first lumen whilewithdrawing said biologic-material-delivering needle.
 9. The methodclaim 1, further comprising: connecting a first injecting member to afirst connecting member of said biologic-material-delivering needle forfluid communication with said first lumen.
 10. The method of claim 9,further comprising: connecting a second injecting member to a secondconnector of said biologic-material-delivering needle for fluidcommunication with said second lumen.
 11. The method of claim 1,wherein: passing a first suspension of biologic material through saidfirst lumen and out of said side ports associated with said first lumenoccurs at a higher pressure than said passing a second suspension ofbiologic material through said second lumen and out of said end portassociated with said second lumen.
 12. The method of claim 1, wherein:said second suspension of biologic material passing through said secondlumen and out of said distal opening has a greater pressure loss thansaid first suspension of biologic material passing through said firstlumen and out of said ports.
 13. A needle, comprising: a needle bodyhaving a proximal end region, a distal end region, and a sidewall; saidneedle body defining a first lumen extending from said proximal endregion to said distal end region; said first lumen terminating in aclosed distal end and communicating with a plurality of ports defined bysaid sidewall; said needle body defining a second lumen extending fromsaid proximal end region to said distal end region and communicatingwith a distal opening in said distal end region; and said distal endregion having a tissue-penetrating tip.
 14. The needle of claim 13,wherein: said first lumen and said second lumen are fixedly positionedto one another.
 15. The needle of claim 13, wherein: said ports arepositioned around the periphery of said needle body.
 16. The needle ofclaim 13, wherein: said ports have a cross-sectional area that issmaller than a cross-sectional area of said distal opening.
 17. Theneedle of claim 13, wherein: said second lumen has a cross-sectionalarea that is smaller than a cross-sectional area of said first lumen.18. The needle claim 13, wherein: said second lumen is positioned withinsaid first lumen.
 19. The needle of claim 18, wherein: said second lumenis surrounded by an annular space.
 20. The needle of claim 13, wherein:a distal end of said second lumen extends beyond a distal end of saidfirst lumen.
 21. The needle of claim 13, further comprising: a plugclosing the distal end of said first lumen.
 22. A fluid deliveringneedle, comprising: a needle body having a proximal end region, a distalend region, a first elongated body, and a second elongated body; saidfirst elongated body having a sidewall defining a first lumen extendingfrom said proximal end region to said distal end region; said firstlumen terminating in a closed distal end and communicating with aplurality of ports defined by said sidewall and positioned around theperiphery of said first elongated body; said second elongated bodypositioned within said first lumen and fixedly coupled to a wallthereof; said second elongated body defining a second lumen extendingfrom said proximal end region to said distal end region andcommunicating with a distal opening in said distal end region; and saiddistal end region of said needle body having a tissue-penetrating needletip.